In the muscarinic binding site, which amino acid participates in hydrogen bonding?

• A. Tryptophan
• B. Aspartic acid 311
• C. Asparagine 617
• D. Serine 200

Answer: (C)

Hydrogen bonding in the muscarinic binding pocket relies on residues whose side chains can both donate and accept hydrogen bonds with the ligand. Acetylcholine presents a carbonyl/ester moiety that can accept hydrogen bonds, and the pocket needs a residue positioned to form a specific, directional H-bond with it. An asparagine side chain has an amide group that can both donate and accept hydrogen bonds, making it well suited to engage the ligand through hydrogen bonding and help orient and stabilize acetylcholine in the binding site. The other residues are more involved in ionic interactions with the positively charged choline (aspartic acid), hydrophobic or aromatic contacts (tryptophan), or general hydrogen bonding that may not be oriented for this particular ligand, so the asparagine stands out as the one capable of forming the essential hydrogen bond in this context.